RESUMO
Dengue virus (DENV) is a mosquito-borne flavivirus that poses a threat to nearly 50% of the global population. DENV has been endemic in Nepal since 2006; however, little is known about how DENV is evolving or the prevalence of anti-DENV immunity within the Nepalese population. To begin to address these gaps, we performed a serologic and genetic study of 49 patients from across Nepal who presented at central hospitals during the 2017 dengue season with suspected DENV infection. Of the 49 subjects assessed, 21 (43%) were positive for DENV NS1 antigen; of these; 5 were also anti-DENV IgM + IgG + ; 7 were DENV IgM + IgG - , 2 were IgM - IgG + , and 7 were IgM - IgG - by specific ELISAs. Seven of the 21 NS1+ sera were RNA+ by RT-PCR (six DENV2, one DENV3), suggesting that DENV2 was the dominant serotype in our cohort. Whole-genome sequencing of two DENV2 isolates showed similarity with strains circulating in Singapore in 2016, and the envelope genes were also similar to strains circulating in India in 2017. DENV-neutralizing antibodies (nAbs) were present in 31 of 47 sera tested (66%); among these, 20, 24, 26, and 12 sera contained nAbs against DENV1, 2, 3, and 4 serotypes, respectively. Serology analysis suggested that 12 (26%) and 19 (40%) of the 49 subjects were experiencing primary and secondary DENV infections, respectively. Collectively, our results provide evidence for current and/or past exposure to multiple DENV serotypes in our cohort, and the RNA analyses further indicate that DENV2 was the likely dominant serotype circulating in Nepal in 2017. These data suggest that expanded local surveillance of circulating DENV genotypes and population immunity will be important to effectively manage and mitigate future dengue outbreaks in Nepal.
RESUMO
OBJECTIVES: Chikungunya and scrub typhus infection are important causes of undifferentiated fever in tropical zones. The clinical manifestations in both conditions are nonspecific and often overlap. This study compares the clinical manifestations and the outcome of chikungunya with chikungunya-scrub typhus coinfection in children. METHODS: A hospital-based observational study was conducted in children below 15 years of age over 16-month duration in 2017-2018. Chikungunya was diagnosed by IgM ELISA. All positive chikungunya cases were subjected to scrub typhus testing, dengue testing, leptospira testing, and malaria testing. Clinical manifestations and outcomes of all patients were recorded. RESULTS: Out of the 382 admitted cases with fever, 11% (n = 42) were diagnosed with chikungunya, and the majority (n = 30, 71.4%) were male. Among the 42 chikungunya cases, 17 (40.5%) tested positive for scrub typhus and one positive for falciparum malaria. Out of a total of 42 chikungunya cases, myalgia, nausea/vomiting, headache, abdominal pain, lymphadenopathy, hepatomegaly, splenomegaly, and edema were 81%, 73.8%, 66.7%, 64.3%, 59.5%, 52.4%, 40.5%, and 38.1%, respectively. Besides, altered sensorium (31%), jaundice (26.2%), dry cough (21.4%), shortness of breath (19%), and seizures (16.7%) were other clinical manifestations present in this group of children. Patients with chikungunya-scrub typhus coinfection reported headaches, pain in the abdomen, dry cough, shortness of breath, seizures, and splenomegaly, significantly more (p value < 0.05) compared to those with chikungunya only. Thirteen (31%) children developed shock, five in the chikungunya group and eight in the chikungunya-scrub typhus coinfection group. Six children in the coinfection group received inotrope. Among the chikungunya-only cases, 22 recovered and one died, whereas in the chikungunya-scrub typhus coinfection group, fourteen recovered and three died. CONCLUSIONS: Both the chikungunya and scrub typhus coinfection groups shared many similar clinical manifestations. In children, coinfection with scrub typhus often leads to modification of the clinical profile, complications, and chikungunya outcome.
RESUMO
Dengue virus (DENV) infection is endemic in Nepal. Although infection rates are reported annually, little information is available about the circulating viral serotypes and genotypes. Here, we report the results of a multicentre cross-sectional study of DENV serotypes and genotypes sampled from individuals with suspected DENV infection in Nepal in 2017. Of the 50 patients sampled, 40 were serologically positive for DENV NS1, 29 for anti-DENV IgM, 21 for anti-DENV IgG and 14 were positive by qRT-PCR. The three serotypes DENV-1, 2 and 3 were detected and there was no DENV-4. Positive samples from serotyping were subjected to PCR amplification by envelope (E) gene specific primer and subsequent bidirectional sequencing of 5 samples. A time to most recent common ancestor phylogenetic tree was constructed from the new sequences obtained here together with historical DENV-1 and DENV-2 E gene sequences. The DENV-1 isolates (n = 2) from Nepalese individuals were closely related to Indian genotype V, whereas DENV-2 isolates (n = 3) belonged to Cosmopolitan genotype IVa, which is closely related to Indonesian isolates. Historical DENV isolates obtained between 2004 and 2013 clustered with Cosmopolitan IVb, Cosmopolitan IVa, and Asian II genotypes. All Nepalese isolates had different lineages with distinct ancestries. With the exception of isolates obtained in 2004, all other previously published isolates had ancestry to geographically distant part of the world. Molecular analysis revealed dengue epidemics to be comprised of different genotypes of serotype 1 and 2 raising concerns on potential role of different genotypes causing Dengue hemorrhagic fever. Also, our result indicated spread of DENV-2 in non-endemic area such as hilly region of Nepal which was considered to be free of dengue due to high altitude and cold weather.
